University of Pittsburgh Department of Biological Sciences Presents:
Friday Noon Seminar Series 2017-2018
Graduate Student: Roni Lahr To Speak
At the heart of cellular growth and proliferation is the ribosome, a multisubunit RNA and protein complex. The generation of the translation machinery is an energetically costly and, therefore, highly regulated process that ensures that protein production meets the demands of the cell. All metazoan ribosomal components are encoded by a class of messages that ensure that each of the 80 ribosomal proteins are generated in a precise temporal and stoichiometric manner. This regulation is accomplished by a cis-regulatory RNA motif within these transcripts called the 5’ Terminal Oligo-Pyrimidine (5’ TOP) motif, which is known to be coordinated by the kinase mTORC1.
In unfavorable conditions, the nutrient-sensing mTORC1 kinase represses ribosome biogenesis through La-related protein 1 (LARP1). LARP1 associates with the TOP motif, but the mechanism by which LARP1 represses TOP translation, however, is unknown. Here we present X-ray crystal structures of the C-terminal DM15 region of human LARP1 complexed with m7GpppC resolved to 1.7 Å. Structural and biochemical data reveal that DM15 region specifically recognizes the invariant m7G and +1C of the 5’TOP motif. DM15 binding occludes the cap-association of translation initiation factors eIF4E and eIF4G. These data define LARP1 as a TOP-selective cap-binding translational repressor and provide a molecular mechanism behind the metabolism of this specific class of important transcripts.
Friday, March 23, 2018
A219B Langley Hall
12:00 PM Seminar